DESCRIPTION (Adapted from the Applicant's Description): Strong epidemiologic evidence has accumulated in recent years to suggest that periconceptional folic acid is an effective agent in reducing the occurrence and recurrence of several common congenital malformations. The metabolic and molecular basis for this preventive effect is completely unknown, and provides a unique opportunity to dissect the interacting etiologic factors that are positively affected by exogenous folic acid. The investigators designed a series of experiments to explore both the nutritional and genetic scope of folate- related factors that may interact in the etiology of neural tube and heart defects. It is hypothesized that common polymorphism in genes coding for critical enzymes in the folate pathway will interact with inadequate maternal micronutrient status to negatively affect the fetal microenvironment, and promote alterations in homeobox gene expression and tissue-specific developmental malformations.